阅读说明：本技术 一种治疗炎性痤疮的凝胶组合物及其制备方法 (Gel composition for treating inflammatory acne and preparation method thereof ) 是由 潘存才 苏江伟 吴万福 张燕 刘建建 郭学平 于 2020-06-24 设计创作，主要内容包括：本申请公开一种治疗炎性痤疮的凝胶组合物,其特征在于,所述凝胶组合物包括：克林霉素或盐酸克林霉素或克林霉素磷酸酯,分子量为100kDa-1200kDa的透明质酸或其盐,和麦角硫因。本申请还公开一种治疗炎性痤疮的凝胶组合物的制备方法,其特征在于,包括以下步骤：将克林霉素或盐酸克林霉素或克林霉素磷酸酯、透明质酸或其盐、以及麦角硫因溶于水中；加入保湿剂和防腐剂,搅拌使其溶解；再加入增稠剂,搅拌使其均匀分散；再加入pH调节剂,调节pH至6-7.5；余量用水补齐,搅拌均匀,即得所述凝胶组合物。所述凝胶组合物可以抑菌消炎、抗氧化,减轻紫外线对患处脆弱皮肤的损伤,促进创口愈合,预防或减少瘢痕的形成。(Disclosed herein is a gel composition for treating inflammatory acne, the gel composition comprising: clindamycin or clindamycin hydrochloride or clindamycin phosphate, hyaluronic acid or salt thereof with molecular weight of 100kDa-1200kDa, and ergothioneine. The application also discloses a preparation method of the gel composition for treating inflammatory acne, which is characterized by comprising the following steps: dissolving clindamycin or clindamycin hydrochloride or clindamycin phosphate, hyaluronic acid or salt thereof and ergothioneine in water; adding humectant and antiseptic, and stirring to dissolve; adding the thickening agent, and stirring to uniformly disperse the thickening agent; adding a pH regulator, and regulating the pH to 6-7.5; and (4) supplementing the balance with water, and uniformly stirring to obtain the gel composition. The gel composition has antibacterial, anti-inflammatory, antioxidant, ultraviolet injury relieving, wound healing promoting, and scar formation preventing or reducing effects.)

1. A gel composition for treating inflammatory acne, said gel composition comprising:

clindamycin or clindamycin hydrochloride or clindamycin phosphate,

hyaluronic acid having a molecular weight of 100kDa-1200kDa or a salt thereof, and

ergothioneine.

2. The gel composition of claim 1, wherein the hyaluronic acid or salt thereof has a molecular weight of 600-700 kDa.

3. The gel composition according to claim 1 or 2, characterized in that it comprises, based on the total weight of the gel composition:

0.2-2% by weight of clindamycin or clindamycin hydrochloride or clindamycin phosphate,

1-10% by weight of hyaluronic acid or a salt thereof, and

0.01-5% by weight of ergothioneine.

4. The gel composition according to any one of claims 1-3, wherein the gel composition comprises, based on the total weight of the gel composition:

0.8-1.2% by weight of clindamycin or clindamycin hydrochloride or clindamycin phosphate,

1.5-5% by weight of hyaluronic acid or a salt thereof, and

0.04-1.5% by weight of ergothioneine.

5. The gel composition according to any one of claims 1 to 4, wherein the gel composition comprises, based on the total weight of the gel composition:

0.8-1.2% by weight of clindamycin or clindamycin hydrochloride or clindamycin phosphate,

1.7-2.5% by weight of hyaluronic acid or a salt thereof, and

0.04-0.07 wt% ergothioneine.

6. The gel composition of any one of claims 1-5, further comprising: thickening agent, humectant and preservative.

7. The gel composition of any one of claims 1-6, further comprising, based on the total weight of the gel composition: 0.3-3 wt% of thickening agent, 5-30 wt% of humectant and 0.1-2 wt% of preservative.

8. The gel composition of claim 6 or 7, wherein the thickener is carbomer, the humectant is glycerin, and the preservative is methylparaben.

9. The gel composition according to any one of claims 1 to 8, wherein the gel composition comprises: clindamycin phosphate.

10. The gel composition of any one of claims 1-9, wherein the gel composition further comprises a pH adjusting agent.

Technical Field

The application belongs to the technical field of cosmetics and medicines, and particularly relates to a gel composition for treating inflammatory acne and a preparation method thereof.

Background

Acne is a common chronic inflammatory disease of pilosebaceous glands, the course of disease is long-lasting and slow to cure, the disease is easy to repeat, abscess is caused in severe cases, and scars are left after healing.

The external medicine for treating acne comprises vitamin A acid medicine and antibiotic medicine, such as lincomycin, Clindamycin, benzoyl peroxide, etc. compared with lincomycin, the antibacterial activity of Clindamycin is enhanced by 4-8 times, and its adverse reaction is low, so that Clindamycin hydrochloride (Clindamycin hydrochloride) is also called Clindamycin hydrochloride, its chemical name is 6- (1-methyl-trans-4-propyl-L-2-pyrrolidine formamido) -1-thio-7-chloro-6, 7, 8-trideoxy-L-threo- α -D-galactopyranose methyl glycoside hydrochloride, and its molecular formula is C₁₈H₃₃ClN₂O₅S & HCl is a semi-synthetic derivative of lincomycin hydrochloride, namely the lincomycin hydrochloride is formed by replacing hydroxyl on C7 position of the lincomycin hydrochloride with chlorine atom after structural modification. Clindamycin phosphate is a semi-synthetic derivative of clindamycin with the chemical name (2S-trans) -6- (1-methyl-4-propyl-2-pyrrolidine carbonamido) -1-thio-methylThe group-7-chloro-6, 7, 8-trideoxy-L-threo- α -D-galactopyranoside-2-dihydrogen phosphate has no antibacterial activity in vitro, but has fat solubility, is easier to be absorbed by skin in comparison with clindamycin, can be rapidly hydrolyzed into clindamycin to show antibacterial activity when entering the body, and has the action mechanism of inhibiting early synthesis of bacterial protein, thereby inhibiting propionibacterium acnes and eliminating inflammation.

Hyaluronic acid is a macromolecular chain polysaccharide consisting of glucuronic acid and N-acetylglucosamine. With the continuous and intensive research, hyaluronic acid and salts thereof are widely applied to the industries of medicines, cosmetics, foods and the like. Research shows that exogenous high-concentration and high-molecular-weight hyaluronic acid can loosen the structure of wound tissue and is beneficial to repair cells such as macrophages and fibroblasts to enter the wound tissue, so that the covering of epithelial cells on the wound surface is accelerated, and the healing process of the wound tissue is promoted. In addition, the content of type III collagen in the wound surface is obviously increased, the diameter of collagen fiber is reduced, and the collagen fiber is arranged loosely and orderly, so that the scar formation in the wound surface healing process is reduced.

Ergothioneine is a natural amino acid occurring in the natural world, which is not synthesized in animals by themselves but can be accumulated in the body by ingestion. It is an effective antioxidant, and can effectively remove active oxygen free radicals, especially hydroxyl free radicals, generated by Propionibacterium acnes metabolism, prevent cells from forming color spots due to peroxidation, increase cell activity, and promote repair.

The existing clindamycin-containing products for treating acne mainly comprise gels, creams and dressings with anti-inflammatory and bacteriostatic effects. Compared with the cream, the gel has the advantages that the gel has good spreadability, is fresh and cool, has no greasy feeling, is easy to clean, and has higher transdermal absorption speed than the cream; compared with external dressing, the gel has certain adhesiveness, is beneficial to the release and absorption of the medicine, and is convenient to use and carry. In terms of therapeutic efficacy, the existing clindamycin-containing products mainly have the effects of inhibiting propionibacterium acnes, eliminating inflammation and promoting wound healing, but do not consider skin cell repair and prevent and reduce scar formation, and the scar formation is usually accompanied by pruritus, stabbing pain and possible later hyperplasia, thereby causing great pain to patients.

Content of application

Aiming at the defects of the prior art, the invention aims to provide a novel clindamycin gel and a preparation method thereof, and the novel gel can inhibit bacteria, diminish inflammation, resist oxidation, relieve the damage of ultraviolet rays to the fragile skin of an affected part, promote wound healing and prevent or reduce the formation of scars in the aspect of treating inflammatory acne. The technical scheme of the application is as follows:

the present application provides a gel composition for treating inflammatory acne, characterized in that said gel composition comprises:

clindamycin or clindamycin hydrochloride or clindamycin phosphate,

hyaluronic acid having a molecular weight of 100kDa-1200kDa or a salt thereof, and

ergothioneine.

2. The gel composition of claim 1, wherein the hyaluronic acid or salt thereof has a molecular weight of 600kDa to 700 kDa.

3. The gel composition according to item 1 or 2, characterized in that it comprises, based on the total weight of the gel composition:

0.2-2% by weight of clindamycin or clindamycin hydrochloride or clindamycin phosphate,

1-10% by weight of hyaluronic acid or a salt thereof, and

0.01-5% by weight of ergothioneine.

4. The gel composition according to any one of items 1 to 3, wherein the gel composition comprises, based on the total weight of the gel composition:

0.8-1.2% by weight of clindamycin or clindamycin hydrochloride or clindamycin phosphate,

1.5-5% by weight of hyaluronic acid or a salt thereof, and

0.04-1.5% by weight of ergothioneine.

5. The gel composition of any of claims 1-4, wherein the gel composition comprises, based on the total weight of the gel composition:

0.8-1.2% by weight of clindamycin or clindamycin hydrochloride or clindamycin phosphate,

1.7-2.5% by weight of hyaluronic acid or a salt thereof, and

0.04-0.07 wt% ergothioneine.

6. The gel composition of any one of claims 1-5, further comprising: thickening agent, humectant and preservative.

7. The gel composition of any of claims 1-6, further comprising, based on the total weight of the gel composition: 0.3-3 wt% of thickening agent, 5-30 wt% of humectant and 0.1-2 wt% of preservative.

8. The gel composition of item 6 or 7, wherein the thickener is carbomer, the humectant is glycerin, and the preservative is methylparaben.

9. The gel composition according to any one of claims 1 to 8, characterized in that it comprises: clindamycin phosphate.

10. The gel composition of any one of claims 1-9, further comprising a pH adjusting agent.

11. The gel composition of any of claims 1-10, wherein the pH adjusting agent is triethanolamine.

12. A method of preparing a gel composition for treating inflammatory acne, comprising the steps of:

dissolving clindamycin or clindamycin hydrochloride or clindamycin phosphate, hyaluronic acid or salt thereof and ergothioneine in water;

adding humectant and antiseptic, and stirring to dissolve;

adding the thickening agent, and stirring to uniformly disperse the thickening agent;

adding a pH regulator, and regulating the pH to 6-7.5;

and (4) supplementing the balance with water, and uniformly stirring to obtain the gel composition.

13. The method of claim 12, wherein the molecular weight of the hyaluronic acid or salt thereof is 600kDa to 700 kDa.

14. The method of item 12 or 13, wherein the gel composition comprises, based on the total weight of the gel composition:

0.2-2% by weight of clindamycin or clindamycin hydrochloride or clindamycin phosphate,

1-10% by weight of hyaluronic acid or a salt thereof, and

0.01-5% by weight of ergothioneine.

15. The method of any one of claims 12-14, wherein the gel composition comprises, based on the total weight of the gel composition:

0.8-1.2% by weight of clindamycin or clindamycin hydrochloride or clindamycin phosphate,

1.5-5% by weight of hyaluronic acid or a salt thereof, and

0.04-1.5% by weight of ergothioneine.

16. The method of any one of claims 12-15, wherein the gel composition comprises, based on the total weight of the gel composition:

0.8-1.2% by weight of clindamycin or clindamycin hydrochloride or clindamycin phosphate,

1.7-2.5% by weight of hyaluronic acid or a salt thereof, and

0.04-0.07 wt% ergothioneine.

17. The method of any one of claims 12-16, wherein the gel composition further comprises: thickening agent, humectant and preservative.

18. The method of any one of claims 12-17, wherein the gel composition further comprises, based on the total weight of the gel composition: 0.3-3 wt% of thickening agent, 5-30 wt% of humectant and 0.1-2 wt% of preservative.

19. The method of claim 17 or 18, wherein the thickening agent is carbomer, the humectant is glycerin, and the preservative is methylparaben.

20. The method of any one of claims 12-19, wherein the gel composition comprises: clindamycin phosphate.

21. The method of any one of claims 12-20, wherein the gel composition further comprises a pH adjusting agent.

22. The method of any one of claims 12-21, wherein the pH adjusting agent is triethanolamine.

Effect of application

The novel gel composition containing clindamycin or clindamycin hydrochloride or clindamycin phosphate is added with hyaluronic acid or salt thereof with the molecular weight of 100kDa-1200kDa and ergothioneine, so that the gel composition can inhibit propionibacterium acnes, eliminate inflammation, remove oxygen free radicals in cells, prevent skin damage cells from keratinizing, improve cell activity, repair cell barriers, play a role in promoting wound healing and preventing and reducing scar formation on inflammatory acne with wounds and even skin injuries, and achieve a better healing effect.

The gel composition for treating inflammatory acne comprises clindamycin or clindamycin hydrochloride or clindamycin phosphate, hyaluronic acid or salt thereof and ergothioneine in the proportion, so that the gel composition has more excellent effect of treating inflammatory acne.

Detailed Description

The following detailed description illustrates and describes embodiments of the present application with reference to specific examples, but the following description should not be construed as limiting the present application in any way.

The present application provides a gel composition for treating inflammatory acne, characterized in that said gel composition comprises:

clindamycin or clindamycin hydrochloride or clindamycin phosphate,

hyaluronic acid having a molecular weight of 100kDa-1200kDa or a salt thereof, and

ergothioneine.

Clindamycin is called clindamycin, belongs to lincomycin medicines, is an artificial semi-synthetic antibiotic, and mainly plays a role by inhibiting the synthesis of bacterial protein. Clindamycin has stronger action and less side effect than lincomycin. Clinically, clindamycin hydrochloride and clindamycin phosphate are used in many forms.

The hyaluronate may be any salt of hyaluronic acid disclosed in the prior art, such as sodium hyaluronate, zinc hyaluronate, silver hyaluronate, calcium hyaluronate, gold hyaluronate, or potassium hyaluronate, preferably sodium hyaluronate.

The molecular weight of the hyaluronic acid or a salt thereof may specifically be 100kDa, 150kDa, 200kDa, 250kDa, 300kDa, 350kDa, 400kDa, 450kDa, 500kDa, 550kDa, 600kDa, 650kDa, 700kDa, 750kDa, 800kDa, 850kDa, 900kDa, 950kDa, 1000kDa, 1050kDa, 1100kDa, 1150kDa, 1200kDa, or the like. In a preferred embodiment, the molecular weight of the hyaluronic acid or salt thereof is between 600kDa and 700 kDa.

In a preferred embodiment, the gel composition includes clindamycin phosphate, which is more readily absorbed transdermally than clindamycin and produces less of an adverse reaction than clindamycin hydrochloride.

In one embodiment, the gel composition comprises, based on the total weight of the gel composition:

0.2 to 2% by weight, preferably 0.8 to 1.2% by weight of clindamycin or clindamycin hydrochloride or clindamycin phosphate, specifically 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2% by weight or the like of clindamycin or clindamycin hydrochloride or clindamycin phosphate;

1 to 10% by weight, preferably 1.5 to 5% by weight, more preferably 1.7 to 2.5% by weight of hyaluronic acid or a hyaluronic acid salt, specifically 1%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10% by weight or the like of hyaluronic acid or a hyaluronic acid salt; and

0.01 to 5% by weight, preferably 0.04 to 1.5% by weight, more preferably 0.04 to 0.07% by weight, of ergothioneine, and specifically may be 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.5%, 0.7%, 1%, 1.3%, 1.5%, 1.7%, 2%, 2.3%, 2.5%, 2.7%, 3%, 3.2%, 3.5%, 3.7%, 4%, 4.2%, 4.5%, 4.7%, 5% by weight, or the like.

In one embodiment, the gel composition comprises, based on the total weight of the gel composition: 0.2-2 wt% of clindamycin or clindamycin hydrochloride or clindamycin phosphate, 1.7-2.5 wt% of hyaluronic acid or a salt thereof, and 0.01-5 wt% of ergothioneine.

In one embodiment, the gel composition comprises, based on the total weight of the gel composition: 0.2-2 wt% of clindamycin or clindamycin hydrochloride or clindamycin phosphate, 1.7-2.5 wt% of hyaluronic acid or a salt thereof, and 0.04-1.5 wt% of ergothioneine.

In one embodiment, the gel composition comprises, based on the total weight of the gel composition: 0.8-1.2 wt% of clindamycin or clindamycin hydrochloride or clindamycin phosphate, 1.5-5 wt% of hyaluronic acid or a salt thereof, and 0.04-0.07 wt% of ergothioneine.

In one embodiment, the gel composition further comprises: thickening agent, humectant and preservative. As the thickener, for example, carbomer, carboxymethylcellulose, poloxamer, etc. can be used. As the humectant, for example, glycerin, propylene glycol, polyethylene glycol, and the like can be used. As the preservative, for example, methylparaben, sorbic acid, chlorocresol, and the like can be used.

In one embodiment, the gel composition further comprises, based on the total weight of the gel composition: 0.3 to 3% by weight of a thickener, specifically 0.3%, 0.5%, 0.8%, 1%, 1.3%, 1.6%, 1.9%, 2.1%, 2.5%, 2.8%, 3.0% by weight; 5 to 30% by weight, and specifically 5%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30% by weight, and the like; and 0.1 to 2% by weight of a preservative, specifically 0.1%, 0.3%, 0.5%, 0.7%, 0.8%, 1%, 1.2%, 1.4%, 1.6%, 1.8%, 2% by weight or the like.

In one embodiment, the gel composition further comprises, based on the total weight of the gel composition: 0.3-1.2% by weight of carbomer, 8-15% by weight of glycerol, and 0.1-0.5% by weight of methylparaben.

In one embodiment, the gel composition further comprises a pH adjuster, which may be triethanolamine, 2% NaOH solution, or the like.

In one embodiment, the gel composition consists of clindamycin or clindamycin hydrochloride or clindamycin phosphate, hyaluronic acid or a salt thereof, ergothioneine, a thickening agent, a humectant, a preservative, a pH adjusting agent, and water.

The application also provides a preparation method of the gel composition for treating inflammatory acne, which is characterized by comprising the following steps:

dissolving clindamycin or clindamycin hydrochloride or clindamycin phosphate, hyaluronic acid or salt thereof and ergothioneine in water;

step two, adding a humectant and a preservative into the solution obtained in the step one, and stirring to dissolve the humectant and the preservative;

step three, adding a thickening agent into the solution obtained in the step two, and stirring to uniformly disperse the thickening agent;

step four, adding a pH regulator into the product obtained in the step three, and regulating the pH to 6-7.5;

and step five, supplementing the balance of water, and uniformly stirring to obtain the gel composition.

In a specific embodiment, in the fourth step, the pH may be specifically adjusted to 6, 6.2, 6.4, 6.6, 6.8, 7, 7.2, 7.4, 7.5, etc., preferably to 7.

In one embodiment, only a small amount of water is added for replenishment in step five, and after replenishment with water, the pH of the gel composition changes very little, between 5.9 and 7.6, preferably between 6 and 7.5, relative to the pH of the product obtained in step four.

In one embodiment, in the third step, the thickener is added into the solution obtained in the second step, and the mixture is stirred for 30 to 60min to uniformly disperse the thickener, preferably for 40 min.

According to the application, hyaluronic acid or salt thereof and ergothioneine are simultaneously added into clindamycin or clindamycin hydrochloride or clindamycin phosphate, the molecular weight of the hyaluronic acid or salt thereof is limited to be 100kDa-1200kDa, and the obtained gel composition can better prevent and reduce scar formation and achieve a better healing effect. Clindamycin or clindamycin hydrochloride or clindamycin phosphate, hyaluronic acid or salt thereof and ergothioneine are added in the content defined in the application, and the pH of the gel composition is further controlled, so that inflammatory acne can be better treated, and scar hyperplasia can be prevented.